We are interested in the dynamic change of protein composition and conformation at the mammalian central nervous system, which eventually leads to structural and functional change of the synapses. In this research project, we have tried to find novel synaptic protein-protein interactions using phage-display screening system. The result reveals the usefulness of the phage display system. It can detect new protein interaction which cannot be detected by conventional two-hybrid assay theoretically, (see below). It is also evident that phage-display system has severe limitations which make this system unable to detect many known interactions. As a conclusion, phage display system is most useful when used in combination with conventional techniques like two-hybrid assay or affinity purificationWe first screened binding partners for NMDA-type glutamate receptor ectodomain or L1 adhesion molecule ectodomain using phage-display system. We found neuron-specific ubiquitin ligase fbx2 as a binding protein. Further analysis reveals that fbx2 recognizes N-linked glycosylation moiety on these ectodomain molecules and is thought to have some role in the quality control system of these membrane moleculesThis result opens up a new possibility : ubiquitin system plays an important role in the control of synaptic proteins. To further examine this possibility, we tested the biological activity of sigh, another ubiquitin ligase identified as a binding protein to metabotropic glutamate receptor by two-hybrid screening. It reveals that siah actually mediates specific ubiquitination and degradation type-I metabotropic glutamate receptorIdentification of these molecules will lead to elucidate the new mechanism in which ubiquitination system precisely controls amount of synaptic molecules and eventually controls overall synaptic response characteristics